AGE–modified albumin containing infusion solutions boosts septicaemia and inflammation in experimental peritonitis
| Autor: | Peter P. Nawroth, Elizabeth K. Deemer, Per M. Humpert, Martin Andrassy, Ezzat M. Awad, Stefan Hofer, Michael Kasper, Angelika Bierhaus, Suzanne R. Thorpe, Markus Schwaninger, Ivan K. Lukic, Markus A. Weigand, Erwin Schleicher |
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| Rok vydání: | 2009 |
| Předmět: |
Glycation End Products
Advanced Receptor for Advanced Glycation End Products Immunology Serum albumin Peritonitis Inflammation Transfection Proinflammatory cytokine Sepsis Mice Peritoneal cavity medicine Animals Humans Immunology and Allergy Receptors Immunologic Infusions Intravenous Aorta Cells Cultured Serum Albumin Mice Knockout biology business.industry Lysine Albumin Endothelial Cells HSA albumin infusion solutions septicaemia inflammation experimental peritonitis Cell Biology medicine.disease Mice Inbred C57BL Solutions Disease Models Animal medicine.anatomical_structure biology.protein Cattle Endothelium Vascular medicine.symptom Primary Research business Infiltration (medical) |
| Zdroj: | Journal of Leukocyte Biology. 86:589-597 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | Advanced glycation endproducts (AGEs) act as potential contaminants of infusion solutions boosting inflammation in experimental sepsis. HSA preparations for i.v. use are administered in critically ill patients. Although increasing intravascular osmotic pressure seems to be a pathophysiologically orientated treatment, clinical trials do not indicate a benefit for mortality in HSA–treated patients. Instead, there is evidence for inflammatory reactions upon infusion of different HSA batches. A neglected issue concerning the safety and quality of these therapeutics is processing–related post–transcriptional protein modifications, such as AGEs. We therefore tested the hypothesis that commercially available infusion solutions contain AGEs and studied whether these protein modifications influence outcome and inflammation in a murine model of sepsis induced by CLP. Screening of different HSA and Ig preparations in this study revealed an up to approximate tenfold difference in the amount of AGE modifications. Application of clinically relevant concentrations of CML–modified HSA in CLP led to increased inflammation and enhanced mortality in wild–type mice but not in mice lacking the RAGE. Lethality was paralleled by increased activation of the proinflammatory transcription factor NF–κB, NF–κB–dependent gene expression, and infiltration of inflammatory cells in the peritoneal cavity. This study implies that infusion solutions containing a high load of the AGE–modified protein have the potential to activate RAGE/NF–κB–mediated inflammatory reactions, causing increased mortality in experimental peritonitis. |
| Databáze: | OpenAIRE |
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